Several forms of synaptic plasticity are expressed as changes in the number of postsynaptic AMPA receptors. The role of AMPA receptors in the induction of synaptic plasticity has however received less attention. Restricted to the developmental period in hippocampal principal neurons, but not in interneurons, we have shown that AMPA receptor activation, either by synaptically released glutamate or by exogenously applied agonist, seems sufficient to induce removal of AMPA receptors from the synapse, resulting in AMPA silent synapses. This synaptic depression is reversible in the absence of AMPA receptor activation, but is stabilized by NMDA receptor-dependent induction of long-term depression. It is also reversed by NMDA receptor-dependent induction of long-term potentiation. These findings indicate that agonist-induced removal of AMPA receptors is an induction mechanism for LTD in developing principal neurons and interneurons.